Higher rate of COVID death before vax linked to common inflammatory immune conditions

 People with certain inflammatory immune conditions affecting the joints, bowel and skin, such as  rheumatoid arthritis, may have been more at risk of dying or needing hospital care if they got COVID-19 before vaccination compared with the general population, according to a new study published in The Lancet Rheumatology.

The findings are based on analysis of 17 million patient GP records in England during the first phase of the pandemic from March-September 2020, when the UK was in lockdown and before vaccines were available. Since then, many of the people treated with medicines analysed in this study have been specifically targeted for third primary vaccine doses followed by boosters and are on a list of people to offered anti-viral treatments.

The study was conducted by a team from the London School of Hygiene & Tropical Medicine (LSHTM) using the OpenSAFELY platform with colleagues from the St John’s Institute of Dermatology at Guy’s and St Thomas’ NHS Foundation Trust, University of Oxford, King’s College London, the University of Exeter and University of Edinburgh.

More than one million patients in the analysis had immune mediated inflammatory diseases (IMIDs). These included inflammatory bowel disease such as Crohn’s disease and ulcerative colitis, conditions affecting the joints such as rheumatoid arthritis, and skin conditions including psoriasis.

After accounting for age, sex, deprivation, and smoking status, the research suggests that people with IMIDs affecting the bowel, joints and skin had a 23% increased risk of COVID-19-related death and 23% increased risk of COVID-related hospitalisation compared to people without IMIDs before the introduction of vaccines and anti-viral treatments. People with inflammatory joint disease appeared to be at greatest risk compared to those with gut or skin disease. Compared to the general population, the risk of death was estimated by the researchers to be approximately eight extra deaths per 1,000 people with joint disease in a year (without taking into account other differences between people with and without joint disease, e.g. age and other health conditions).

Study author Professor Sinéad Langan, Wellcome Senior Clinical Fellow and Professor of Clinical Epidemiology at LSHTM, said: “During the height of the pandemic in England in 2020, many people with inflammatory conditions affecting the bowel, joints and skin were advised to stay at home and shield because doctors did not know how COVID-19 would affect them, or what the effects of drugs such as immune modifying therapies used to treat IMIDs would be.

“Our study provides the most accurate assessment of risk of severe COVID-19 before vaccination in people with IMIDs and with the drugs used for their treatment. We hope this analysis will help to inform evidence-based policy as we continue to live with COVID-19.”

The team also investigated the impact of certain medication, identifying around 200,000 people who were on immune modifying drugs. The study found there was no overall increased risk of COVID-19 death or hospitalisation for patients on most targeted immune modifying drugs (often referred to as biologics) compared to standard systemics (that work on the wider immune system) given to treat this group of conditions. For example, there was no increase in severe COVID-19 infections (death, critical care admission or death, or hospitalisation) in people taking most of the targeted immune modifying therapies examined — including TNF blockers such as adalimumab — compared to more commonly used standard immune suppressants such as methotrexate.

Professor Catherine Smith, consultant dermatologist at St John’s Institute of Dermatology at Guy’s and St Thomas’ NHS Foundation Trust, said: “We know that certain factors, such as being older, increase a person’s risk of suffering severe COVID-19 infection. But until now we did not know whether severe COVID-19 risk increases with ongoing health conditions related to problems with the immune system such as arthritis, Crohn’s disease and psoriasis.

“Our study provides important information that will help guide policymakers to ensure prevention strategies such as vaccination, and early intervention treatments such as anti-virals are targeted towards those most at risk. 

“Overall our findings with respect to immune-modifying drugs are reassuring. It’s important that people continue to take prescribed medication and discuss treatment decisions with their physicians and getting vaccines according to recommendations.”

The OpenSAFELY platform accesses an unprecedented scale of data accessed through a Trusted Research Environment to preserve an individual’s privacy. It provides the full dataset of all raw, single-event-level clinical events for all individuals at 40% of all GP practices in England, including all tests, treatments, diagnoses, and clinical and demographic information linked to various sources of hospital data including, for the first time, a comprehensive dataset of medications supplied by hospitals.

This study was made possible through OpenSAFELY links to a new source of data with information on “high cost” drugs. Due to the way these specialist drugs are prescribed, for example through schemes via home care companies, this means they are not usually on GP records. The study marks the first time researchers have been able to analyse this group of drugs in this way, and highlights why access to these data is critical for research.

Co-author Dr Nick Kennedy, Consultant Gastroenterologist and Clinical Senior Lecturer at the University of Exeter, said: “Our study is an example of the high quality, collaborative research that has taken place during the pandemic using OpenSafely’s innovative research platform. For patients with inflammatory bowel disease, the overall message is reassuring, although there was some increase in the risk of being hospitalised in those who had COVID-19.

“Our research also shows that the targeted drugs we commonly use to treat Crohn's and colitis are not associated with increased risk of poor outcomes.”

The authors acknowledge limitations of the study including the fact that people with these conditions may have shielded or avoided infection with COVID-19 and that other health issues such as cardiovascular disease and diabetes may affect COVID-19 outcomes for people with IMIDs, as well as the potential for misclassification of prescriptions or medication on the patient records.

This study was supported by funding to the researchers from the UK Medical Research Council and Wellcome Trust.

For media enquiries or to request interviews contact press@lshtm.ac.uk

Publication:

Brian MacKenna*, Nicholas A Kennedy*, Amir Mehrkar*, Anna Rowan*, James Galloway*, Julian Matthewman*, Kathryn E Mansfield, Katie Bechman, Mark Yates, Jeremy Brown, Anna Schultze, Sam Norton, Alex J Walker, Caroline E Morton, David Harrison, Krishnan Bhaskaran, Christopher T Rentsch, Elizabeth Williamson, Richard Croker, Seb Bacon, George Hickman, Tom Ward, Simon Davy, Amelia Green, Louis Fisher, William Hulme, Chris Bates, Helen J Curtis, John Tazare, Rosalind M Eggo, David Evans, Peter Inglesby, Jonathan Cockburn, Helen I McDonald, Laurie A Tomlinson, Rohini Mathur, Angel Y S Wong, Harriet Forbes, John Parry, Frank Hester, Sam Harper, Ian J Douglas, Liam Smeeth, Charlie W Lees, Stephen J W Evans†, Ben Goldacre†, Catherine Smith†, Sinéad M Langan†, Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune modifying therapies: a nationwide cohort study in the OpenSAFELY platform. The Lancet Rheumatology.

https://www.eurekalert.org/news-releases/955314

Tenn. Gov. Signs Exec Order To Enhance School Safety, Calls For 'Single Point Of Entry'

 by Mimi Nguyen Ly via The Epoch Times (emphasis ours),

Tennessee Gov. Bill Lee signed an executive order on Monday to ensure working safety protocols at schools, and to evaluate training for law enforcement for handling active shooter scenarios, in a bid to fortify school security across the state after the recent mass shooting at a school in Texas in which 21 people were killed.

“Parents need to have full confidence that their children are safe at school, and thankfully, Tennessee has built a firm foundation with our practical approach to securing schools, recognizing crisis, and providing confidential reporting of any suspicious activity,” Lee, a Republican, said in a statement.

For parents, the executive order (pdf) creates a “School Safety Resources and Engagement Guide” to provide parents with information about how to report suspicious or concerning activity to school administrators and local law enforcement. The guide would also help parents inquire about building security and compliance at their child’s school, and provides parents ways to access mental health resources for their child.

Lee in the order called on parents and the community to work with law enforcement to ensure simple practices, such as “ensuring a single point of entry and multiple points of exit, securing vestibules and other access points, and reporting suspicious activity.”

Tennessee state agencies will also provide more guidance to help local school districts implement current school safety law. Under the law, public schools are required each year to carry out a school security assessment and submit a safety plan to the state’s school safety center.

The guidance will include more frequent audits of local school security assessments and safety plans, and will also provide a set of “best practices” for school leaders to enhance the security of a building against an intruder.

Among a slew of other measures, the executive order will ensure that educators, school leaders, and staff will have additional training and educational materials no later than Aug. 1.

For law enforcement, the executive order directs the Tennessee Department of Commerce and Insurance to “evaluate and assess law enforcement training standards” and to recommend improvements to existing training for active-shooter scenarios. The department must provide a report to the governor by July 1.

The executive order will also direct the same department to “review the use of armed security guards in non-public schools” and, with the Tennessee Department of Safety and Homeland Security, report to the governor regarding “the need for active-shooter training for armed guards.”

At a press conference on Monday, Lee was asked by reporters multiple times about the issue of gun laws and gun violence.

“There are a lot of conversations that are happening all across the country about laws that affect gun ownership and red flag laws, and waiting-period laws. And there will be those conversations all across the country. We’re not looking at gun restriction laws in my administration right now,” Lee said. “One thing to remember—criminals don’t follow laws. Criminals break laws. Whether they are a gun law, a drug law, criminals break laws. We can’t control what they do but we can control what we can control and that’s what we’re working on today.”

Separately, he said, “Certainly, gun violence is a serious problem in our country, and it has been a rising problem in our country.” He noted that gun violence is just one aspect of violent crime. “Crime is a problem,” he said.

When asked again about the administration’s actions on gun laws, he said: “We are not talking in our administration about gun laws, gun registries. We’re working on school safety, and what’s been laid out and what’s been laid out in this plan today.”

The May 24 Robb Elementary shooting in Uvalde, Texas, resulted in the deaths of 19 students and two teachers. Officials said an 18-year-old shooter entered the school via a back door that was unlocked.

Uvalde Consolidated Independent School District Police Chief Pete Arrendondo became the target of accusations that he was responsible for a delayed police response to the shooting, after it was revealed that officers, after having entered the building, waited about 45 minutes to breach the classroom where the shooter, as well as students and teachers, were.

Texas Department of Public Safety Director Steven McCraw said that Arrendondo held back officers from immediately breaching the classroom because he thought the situation was a barricaded suspect, not an active-shooter one.

https://www.zerohedge.com/political/tennessee-governor-signs-executive-order-enhance-school-safety-calls-single-point-entry

10-Year Data Support Supplements for Macular Degeneration

 The Age-Related Eye Disease Study 2 (AREDS2) formula of vitamins and minerals remains safe and effective in treating age-related macular degeneration (AMD) over 10 years, researchers say.

Replacing beta carotene with lutein and zeaxanthin appeared to eliminate the increased risk of lung cancer seen with the original AREDS formula while achieving an increase in effectiveness, said Emily Chew, MD, director of the Division of Epidemiology and Clinical Applications at the U.S. National Eye Institute in Bethesda, Maryland.

She recommended that everyone with intermediate- or late-macular degeneration take the AREDS2 supplements, which are available over the counter. “I think that really confirms that this is the right formulation for safety and for beneficial effects,” she told Medscape Medical News.

The increased lung cancer risk with beta carotene mostly applies to smokers and former smokers, Chew said.

Launched in 1996, the original AREDS study was the largest trial of dietary supplements ever conducted for macular degeneration.

Chew and her colleagues concluded that the formulation (500 mg vitamin C, 400 international units vitamin E, 2 mg copper, 80 mg zinc, and 15 mg beta carotene) could significantly slow the progression of AMD from moderate to late disease.

But while the researchers were working on the AREDS trial, studies published on beta carotene for the prevention of cancer and cardiovascular disease showed that the vitamin increased the risk of cancer in smokers.

In a new trial, AREDS2, Chew and her team replaced the beta carotene in their formulation with 10 mg lutein and 2 mg zeaxanthin. Like beta carotene, lutein and zeaxanthin are antioxidants that help protect the retina from damage caused by exposure to light.

Lower Risk, More Protection

For AREDS2, launched in 2006, the researchers gave the formulation with beta carotene only to participants who were not current smokers or had stopped smoking for at least 1 year.

At the end of the 5-year AREDS2 study, the researchers concluded that lutein and zeaxanthin did not increase risk for lung cancer, and that the new formulation could reduce the risk of AMD progression by about 25%.

On the other hand, those participants taking the formulation with beta carotene had twice the risk of lung cancer, with most of the cases in former smokers.

The researchers then offered all participants the AREDS2 formulation that included lutein and zeaxanthin instead of beta carotene.

For their latest report, Chew and her colleagues analyzed who among these participants had progressed to late AMD and who had been diagnosed with lung cancer over the 5 years after AREDS2 concluded in 2011.

They were able to collect data on 3882 of the original 4203 AREDS2 participants. All the participants had switched to lutein and zeaxanthin. Yet among those who had originally taken the beta carotene, the incidence of lung cancer was 2.8% vs 1.5% among those who did not take beta carotene (odds ratio 1.82; 95% CI, 1.06-3.12).

And in the group originally assigned to receive lutein and zeaxanthin, the rate of progression to late AMD was 20% lower than in the group originally assigned to receive beta carotene (hazard ratio 0.80; 95% CI, 0.68-0.92).

The researchers also looked at the effects of adding two omega-3 fatty acids to the formulation: docosahexaenoic acid and eicosapentaenoic acid. They found no effect on the progression to late AMD.

Other Dietary Protection

“The results are good, because they will improve the way that physicians can provide some cue to patients by saying that they should take the AREDS2 formulation, including lutein and zeaxanthin instead of beta carotene,” said Serge Camelo, PhD, who researches treatments for macular degeneration at Biophytis, a pharmaceutical company in Paris, France. He was not involved in this study.

On the other hand, he pointed out, about half the study participants progressed from moderate to late AMD even while taking the AREDS2 formulation. “So on one hand, it's a good thing that they improved the formulation that they give to patients, and it's safer and better,” he told Medscape. “But there is still a lot of progress to be done in the field.”

One way people with AMD can further slow the progression of AMD is by adhering to the Mediterranean diet, which includes a high proportion of fruits, vegetables, and fish. Fish appeared particularly important, Chew said, citing a separate study.

The diet and the supplements appear to complement each other, she said. While the supplements are most effective in slowing progression to the wet form of AMD, the diet is most effective in slowing progression to the dry form, Chew said.

And unlike the supplements, which are only effective in moderate and late-stage AMD, the Mediterranean diet can reduce the risk of AMD in people without AMD and people in early stages, she said.

The amount of beta carotene in food is not enough to pose a risk of cancer, Chew said.

Chew reported no relevant financial interests. Camelo reported researching treatments for macular degeneration. The study was funded by the National Institutes of Health, which has a royalty-bearing license issued to Bausch and Lomb for the AREDS2 supplements. Bausch and Lomb provided the supplements for the 5-year follow-up study.

JAMA Ophthalmology. Published online June 2, 2022. Abstract.

https://www.medscape.com/viewarticle/975239

Data breach at health care organization may affect 2 m

 A digital attack on a Massachusetts-based health care organization may have compromised the personal information of as many as 2 million people, officials said.

Shields Health Care Group Inc., which provides imaging and ambulatory surgical services at dozens of locations, said in a notice on its website Tuesday that data including names, Social Security numbers, dates of birth, and medical or treatment details is among the information that may have been compromised.

The breach has been reported to federal law enforcement and the U.S. Department of Health and Human Services Office for Civil Rights. That agency reported on its website that 2 million people were affected. An FBI spokesperson said the agency had no comment.

Shields said it “was alerted to suspicious activity that may have involved data compromise” on March 28 and immediately started investigating.

“This investigation determined that an unknown actor gained access to certain Shields systems from March 7, 2022 to March 21, 2022,” the company said. “Furthermore, the investigation revealed that certain data was acquired by the unknown actor within that time frame.”

There is no evidence to indicate that any of the compromised information has been been used to commit identity theft or fraud, Shields said in a statement Wednesday.

“Shields takes the confidentiality, privacy, and security of information in our care seriously,” the website notice said. “Upon discovery, we took steps to secure our systems, including rebuilding certain systems, and conducted a thorough investigation to confirm the nature and scope of the activity and to determine who may be affected.”

The company’s review continues, and once it is complete, people directly affected will be notified, officials said.

Quincy-based Shields has about 40 locations, mostly in Massachusetts but also in New Hampshire and Maine.

Shields also included a list of dozens of facility partners that may have been affected, including Tufts Medical Center, Central Maine Medical Center and UMass Memorial.

FBI Director Christopher Wray this month told a Boston College cybersecurity conference that the agency had thwarted a planned attack on Boston Children’s Hospital that was to have been carried out by hackers sponsored by the Iranian government.

Health care is classified by the U.S. government as one of 16 critical infrastructure sectors, and health care providers are seen as ripe targets for hackers.

https://apnews.com/article/technology-health-us-department-of-and-human-services-boston-massachusetts-4aed357bc7f3fd0a8a88f40d13985fdf

US 'diverts COVID-19 funds to secure vaccines' amid stalemate

 The Biden administration said Wednesday that a funding crunch is forcing it to divert more than $10 billion in coronavirus relief from test procurement and other efforts as it tries to come up with money to secure the next generation of vaccines and treatments for some high-risk Americans.

The White House said it has been left with “no choice” but to cut back on orders of at-home rapid tests that have supported a domestic manufacturing base for the easy diagnostic tests. It also is scaling back funding for research and development of new COVID-19 vaccines and limiting orders of personal protective equipment in an effort to maintain some stockpiles of vaccines and treatments for Americans heading into the winter.

Even then, the Democratic administration says, there will only be enough money available to provide treatments and vaccines to some people. It urged Congress to act to provide enough money to secure doses for all who might want or need them.

“The administration has to act because Congress won’t,” the White House said in a statement. “These trade-offs we are being forced to make because of Congress will have serious consequences on the development of next-generation vaccines, therapeutics and diagnostics, domestic vaccine production capacity, stockpiling of PPE and the procurement of tests and testing supplies for federally qualified and community health centers.”

The White House said the “unacceptable” trade-offs were due to congressional inaction.

It was not immediately clear which vaccines and treatments the administration was seeking to secure with the limited funding — including whether the administration was placing orders for potential multivalent vaccines that would protect against both the original COVID-19 strain and offer targeted protection against some variants. The White House also didn’t say how many doses of vaccines would be acquired, citing contracting requirements for the lack of clarity.

The administration said the Wednesday moves would shift $5 billion to buy COVID-19 vaccine doses for the fall, $4.9 billion for 10 million Paxlovid oral antiviral treatment courses and $300 million for the purchase of additional monoclonal antibody treatments.

The Biden administration has been warning for months of the potential for rationing and other tough trade-offs if Congress doesn’t act to provide additional funding, saying that it would cost lives as people’s immunity from booster doses or from prior infection wane.

Lawmakers in March appeared near a deal for $10 billion of the $22.5 billion that President Joe Biden has requested, but negotiations broke down over Biden’s plans to end pandemic-related public health restrictions on U.S. borders that severely curtailed migration. Though that move has been blocked by a federal judge, lawmakers have appeared no closer to reaching a deal.

The White House has said that if it doesn’t act swiftly to secure vaccines, other nations will lock in their own places in line ahead of the U.S. That would reverse the trend of the U.S. being among the first nations, if not the first nation, to market vaccines and life-saving COVID-19 treatments like Paxlovid.

https://apnews.com/article/covid-health-congress-government-and-politics-237a94c5400216503c24d524c04b29da

Walgreens Sues Hospital Over New In-House Pharmacy

 Walgreens has filed a lawsuit against Hagerstown, Maryland-based Meritus Health after the community hospital and health system opened an independent pharmacy in the lobby of its flagship medical center.

The retail pharmacy giant alleged that by opening an 1,800-square-foot pharmacy inside Meritus Medical Center (MMC), the health system is in violation of its lease agreement, which promised no other pharmacy would be established on the Robinwood medical campus, where MMC is both located.

But Meritus claimed the 2013 lease agreement is no longer valid, since the unit currently leased by Walgreens was sold to another company and is no longer part of the Meritus portfolio.

Maulik Joshi, DrPH, president and CEO of Meritus Health, told MedPage Today that the company opened its own pharmacy for better continuity of care, to ensure that patients who are discharged can get any medications before they leave the building.

"Our mission is to improve the health of our community," Joshi said. "We're doing this for our community."

In its complaint, filed May 13, Walgreens argued that selling the unit "was a bad faith attempt by Meritus to avoid having to comply with the exclusivity obligation imposed by the [lease contract]." It alleged that Meritus sold the unit to Water Street Investments LLC, whose "managing member ... is a physician affiliated with Meritus."

Joshi said the physician "to which we believe the complaint refers ... is a community physician (not employed) with Meritus medical staff membership. Almost all the community physicians have medical staff membership and/or privileges at the hospital."

In a press release shared with MedPage Today, Joshi called the lawsuit a "tough pill to swallow." The release noted that "Walgreens is one of the largest for-profit corporations in the country, and, according to their Q2 2022 SEC filing, had Net Earnings of over $4.3 billion for the six months ending February 28, 2022."

Joshi said Meritus is a 100-year-old independent, non-profit community organization, with the 327-bed MMC as its flagship facility on the Robinwood campus. The system is the sole provider for Washington County, Maryland, which has more than 150,000 residents.

Walgreens argued in its complaint that it will suffer "substantial, immediate, and irreparable harm" due to the new pharmacy. "The operation of the Meritus Pharmacy poses a significant and substantial threat to Walgreens' business because it directly competes with and is substantially similar to the Walgreens Pharmacy," the complaint stated.

A spokesperson for Walgreens declined to comment for this story, given the pending litigation.

Meritus has since filed a motion to dismiss the lawsuit, alleging that Walgreens' claims fail essentially because Meritus has been released of any obligations as landlord when the unit was sold.

"Meritus had the absolute unfettered right to sell [the unit] to a new owner without the consent of Walgreens and did so, and, upon that sale and transfer of the ownership of [the unit] to a new owner, Meritus was relieved of all obligations thereafter arising expressed in the Lease or implied by law," the filing stated.

https://www.medpagetoday.com/special-reports/exclusives/99119

Radius Health Update on Abaloparatide Transdermal System

 

• Company ascertained regulatory clarity for possible forward progression of abalo-TDS
• Additional and successful clinical trial would be required to advance towards an NDA filing
• New timeline for earliest possible abalo-TDS launch: 2H 2025
• Based on regulatory clarity, timeline, and costs, Radius will cease all work on the program
• Eliminates prospective program costs: $100+ million over 3+ years: CMC, clinical, and launch
• Company continues to dynamically manage capital and its allocation, risk, and overall timelines

Radius Health, Inc. (“Radius” or the “Company”) (NASDAQ: RDUS) provided an update on the abaloparatide transdermal system (abalo-TDS) development program.

As previously reported on December 8, 2021, the Phase 3 results for abalo-TDS did not meet its primary endpoint of non-inferiority to abaloparatide subcutaneous injection (TYMLOS). The data for spine BMD vs. baseline showed abalo-TDS had a 7.1% increase vs. TYMLOS +10.9%, both considered clinically meaningful. Despite missing the non-inferiority margin, the transdermal system demonstrated a bone building benefit to patients.

Following the reported Phase 3 trial results, the Company outlined three requirements needed to move the abalo-TDS program forward. Those were regulatory clarity, a re-constructed supply chain and CMC agreement/economics and lastly, external funding.

Since December we have completed both our internal analysis and sought regulatory feedback on possible paths forward for abalo-TDS. We committed to providing clarity to the market by June of 2022.

Regulatory feedback from the U.S. Food and Drug Administration (FDA) on abalo-TDS indicated an additional pivotal trial would be required to move forward with any regulatory filings. If successful, we would then incorporate the newly generated data in a filing for future consideration by the FDA with the earliest possible launch timeline of 2H 2025.

Given the clarity on the regulatory pathway, delayed commercial timelines, and $100+ million of additional capital required over the next 3+ years, Radius will cease all work on abalo-TDS.

We remain open to third party interest in the abalo-TDS product opportunity which could fit well with both traditional as well as non-traditional counterparties whose business is focused on the primary care market.

https://ir.radiuspharm.com/news-releases/news-release-details/radius-health-update-abaloparatide-transdermal-system